1a.Objectives (from AD-416):
Vitamin D deficiency causes loss of bone mineral density by impairing calcium and phosphate absorption. Parathyroid hormone (PTH) is a principal mediator of this effect of vitamin D and elevated PTH can be an indicator of vitamin D deficiency. In a just-completed study with the same research group we found that vitamin D supplementation improved vitamin D “status” in that serum vitamin D levels increased and serum PTH decreased, as expected. Interestingly, PTH decreased in subjects with “normal” vitamin D status. These subjects were HIV infected and were taking tenofovir (TDF)-containing anti-retroviral therapy. This observation suggested that TDF produced a functional vitamin D deficiency, requiring higher serum vitamin D levels to maintain “normal” PTH levels. Fibroblast growth-factor 23 (FGF23) mediates phosphate balance and changes in FGF23 (not measured originally) may explain some of the negative effects of TDF on calcium and phosphate balance, and the relationship of vitamin D to PTH. For this reason we propose to measure FGF-23 in serum samples from the just-completed study to address this question.
1b.Approach (from AD-416):
Our research plan is to measure serum FGF23 (and some related markers of vitamin D metabolism and kidney function) in previously collected serum located at the WHNRC. Data analysis will be performed with research collaborators at a Westat, Medical College of Wisconsin and UCSF.
This agreement supports Objective 1 of the in-house project with the goal of determining if inflammation and drugs that alter kidney function affect the metabolism of vitamin D and thus can affect calcium balance and bone mineralization. The purpose of this project is to determine if the plasma concentration of fibroblast growth factor (FGF)-23, markers of “free” plasma calcitriol (the active metabolite of vitamin D), and markers of kidney tubule function are altered in subjects from a previous intervention trial that administered vitamin D3 (50,000 IU/month) vs. placebo to HIV-positive adolescents and young adults receiving and not receiving the antiretroviral tenofovir (TDF). Both HIV infection and TDF adversely affect bone mineral density, perhaps by affecting vitamin D and calcium metabolism. The overall aim of the trial was to determine if improving vitamin D status would improve markers of calcium nutrition (principally plasma parathyroid concentration) and bone metabolism. Laboratory work has been completed and data analysis is in progress. Laboratory work is being conducted at the WHNRC and progress is being monitored by regular face-to-face meetings between the principal investigator and project staff.